Diseased Tendon Models Demonstrate Influence of Extracellular Matrix Alterations on Extracellular Vesicle Profile DOI Creative Commons

Kariman A. Shama,

Zachary Greenberg,

Chadine Tammame

et al.

Bioengineering, Journal Year: 2024, Volume and Issue: 11(10), P. 1019 - 1019

Published: Oct. 12, 2024

Tendons enable movement through their highly aligned extracellular matrix (ECM), predominantly composed of collagen I. Tendinopathies disrupt the structural integrity tendons by causing fragmentation fibers, disorganization fiber bundles, and an increase in glycosaminoglycans microvasculature, thereby driving apparent biomechanical regenerative capacity patients. Moreover, complex cellular communication within tendon microenvironment ultimately dictates fate between healthy diseased tendon, wherein vesicles (EVs) may facilitate tendon's transporting biomolecules tissue. In this study, we aimed to elucidate how EV functionality is altered context microenvironments using polycaprolactone (PCL) electrospun scaffolds mimicking pathological matrices. Scaffolds were characterized for alignment, mechanical properties, activity. EVs isolated analyzed concentration, heterogeneity, protein content. Our results show that our mimicked led secretion baseline metabolic activity over where reduced a significant 5 days observed. These findings suggest scaffold mechanics influence functionality, offering insights into homeostasis. Future research should further investigate cargo affects microenvironment.

Language: Английский

Microenvironmental Modulation for Therapeutic Efficacy of Extracellular Vesicles DOI Creative Commons

Bilu Xiang,

Shiying Zhang, Irene Shuping Zhao

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Extracellular vesicles (EVs) hold significant promise for the prevention and treatment of various diseases. However, translation EV‐based therapies into clinical practice faces considerable challenges, particularly in terms production yield therapeutic efficacy. Recent studies have emphasized heterogeneity EVs influence parental cell microenvironmental signals on their biogenesis, cargo composition, outcomes. This review offers a comprehensive overview strategies to optimize efficacy through physical, biochemical, mechanical modulation. Additionally, it explores how affect EV cargoes mechanisms by which these can improve The also addresses current challenges potential solutions accelerate therapies. Ultimately, highlights modulation unlocking full capacity EVs, providing key insights use treating

Language: Английский

Citations

1
Microbead Encapsulation Strategy for Efficient Production of Extracellular Vesicles Derived From Human Mesenchymal Stem Cells DOI Creative Commons
Yunxia Hu, Lijuan Zheng, Zheng Zheng

et al.

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(4)

Published: April 1, 2025

ABSTRACT Human mesenchymal stem cell‐derived extracellular vesicles (hMSC‐EVs) have shown great potential in tissue repair and regeneration. However, their scalable production functional quality are still limited by current expansion technologies. In this study, we propose a technology for hMSC‐EVs based on three‐dimensional (3D) microbead culture, which enhances the secretory behaviour of hMSC. Fixed number MSCs were encapsulated Matrigel at appropriate densities printed into 3D microbeads custom automated microfluidic bead‐jet printing technique. Compared with 2D culture group, EVs derived from hMSC had smaller size increased yield 20‐fold, actin depolymerisation cell may be an important mechanism enhancing EV secretion. Further analysis confirmed that exhibited enhanced angiogenic proliferative capabilities, promoted viability tube‐forming capacity human umbilical vein endothelial cells (HUVEC). conclusion, encapsulation therapeutic effect provides platform regenerative therapies.

Language: Английский

Citations

1
Mesenchymal stem cell extracellular vesicle vascularization bioactivity and production yield are responsive to cell culture substrate stiffness DOI Creative Commons

Emily H. Powsner,

Stephanie M. Kronstadt,

Kristin Nikolov

et al.

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: 10(3)

Published: Jan. 7, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC EVs) are an attractive therapeutic option for regenerative medicine applications due to their inherently pro-angiogenic and anti-inflammatory properties. However, reproducible cost-effective production of highly potent MSC EVs is challenging, limiting translational potential. Here, we investigated whether the well-characterized responsiveness MSCs mechanical environment-specifically, substrate stiffness-could be exploited generate with increased bioactivity without need biochemical priming or genetic manipulation. Using polydimethylsiloxane bone marrow-derived (BM-MSCs), show that decreasing stiffness substrates as low 3 kPa significantly improves measured by tube formation gap closure assays. We also demonstrate lower EV overall yield, important clinical translation. Furthermore, establish mechanoresponsiveness induced pluripotent (iMSC) comparability BM-MSC EVs, again using With this data, confirm iMSCs' feasibility alternative, renewable cell source reduced donor variability. Overall, these results suggest utilizing a promising, simple, potentially scalable approach does not require exogenous cargo extraneous reagents EVs.

Language: Английский

Citations

0
Matrix stiffness modulated release of spheroid-derived extracellular vesicles and discovery of Piezo1 cargo DOI Open Access
Maulee Sheth, Manju Sharma, Supasek Kongsomros

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract Augmented extracellular matrix (ECM) stiffness is a mechanical hallmark of cancer. Mechanotransduction studies have extensively probed the mechanisms by which ECM regulates intracellular communication. However, influence on intercellular communication aiding tumor progression in three-dimensional microenvironments remains unknown. Small vesicles (EVs) are communicators altered biophysical cues to distant sites through EV-ECM interactions and EV-mediated recipient cell-ECM interactions. Here we demonstrate stiffness-mediated modulation small EVs secretion cargo from oral squamous cell carcinoma spheroids. Using spheroid culture platform with varying properties, show that carry parental biomolecular cargo, including mechanosensitive Piezo1 ion channel adhesion molecule CD44. We comprehensively validate presence both markers our EV populations using proteomic genetic analysis. Transcriptomic analysis microRNA long non-coding RNA released soft stiff spheroids revealed enrichment tumorigenic metastatic profiles cultures compared ones. Gene set comparative dataset obtained overlaying mRNA miRNA identified key oncogenic pathways involved cell-EV crosstalk model.

Language: Английский

Citations

0
Bioprinting with Kidney Derived-Ecm for Extracellular Vesicle-Based Advanced Therapies DOI
Rita Quinteira, Sara Gimondi, Maria Elena Melica

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Soy Protein-Cultured Mesenchymal Stem Cell-Secreted Extracellular Vesicles Target the Neurovascular Unit: Insights from a Zebrafish Brain Injury Model DOI Creative Commons

T.F. Lin,

Pei‐Ying Hsieh,

Hui-Jen Lin

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Cerebral vascular disorders often accompany hypoxia-induced brain injury. In this study, we develop a zebrafish model of cerebral injury to replicate the associated phenotypic changes, including cerebrovascular damage, neuronal apoptosis, and neurological dysfunction. We then explored therapeutic potential extracellular vesicles derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) cultured on soy protein-coated surfaces. These demonstrated superior recovery efficacy, especially in restoring blood–brain barrier integrity improving function. Our findings suggest that these potent vesicles, easily produced WJ-MSCs presence proteins, may mitigate by decreasing severity disorder caused oxidative stress. Protein–protein interactome analysis further suggests multiple signaling pathways are likely involved normal neurovascular unit

Language: Английский

Citations

0
SHP099-containing multi-targeting hydrogel promotes rapid skin reconstruction through modulating a variety of cells DOI Creative Commons

Zhixiao Liu,

Lei Chen, Bingbing Hao

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 7, 2025

Adult wound scarring result in functional skin deficits. However, the development of effective measures to modulate entire healing encourage function reconstruction is still a clinical challenge, as multiple cells are involved hierarchically. Hydrogel scaffolds with long-lasting local release provide new insights into relevance healing. Herein, multi-targeting hydrogel loaded SHP099 (Gel-SHP) designed during repair. Our results show that Gel-SHP promotes rapid by modulating macrophages inflammatory stage, fibroblasts regeneration stage and smooth muscle remodelling stage. could increase M2 macrophage differentiation remodel dermal shell hair follicles through situ release. Moreover, may myofibroblasts promote contraction SHP099-scaffold synergistic interactions. design hydrogels for tissue applications. promising tool clues research paradigms future studies understanding process formation.

Language: Английский

Citations

0
Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders DOI Open Access
Anyuan Zhang, Qiubai Li, Zhichao Chen

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 225 - 225

Published: Dec. 30, 2024

The global issue of aging populations has become increasingly prominent, thus the research and development for anti-aging therapies to assure longevity as well ameliorate age-related complications is put high on agenda. young humoral milieu been substantiated impart youthful characteristics aged cells or organs. Extracellular vesicles (EVs) are a heterogeneous group cell-derived membrane-limited structures that serve couriers proteins genetic material regulate intercellular communication. Of note, EVs appeared be an indispensable component blood in prolonging lifespans, circulating have indicated mediate beneficial effect aging. Human umbilical cord mesenchymal stem (HUCMSC-EVs), isolated from youngest adult cell source, speculated reproduce function partially revitalize numerous organs old animals. Robust evidence suggested HUCMSC-EVs muti-target therapeutic agents combating alleviating degenerative disorders. Here, we provide comprehensive overview effects brain, heart, vasculature, kidney, muscle, bone, other Furthermore, critically discuss current investigation engineering strategies HUCMSC-EVs, intending unveil their full potential field research.

Language: Английский

Citations

3
Mesenchymal Stem Extracellular Vesicles in Various Respiratory Diseases: A New Opportunity DOI Creative Commons

Ziyuan Hu,

Lujian Zhu, Yanglin Zhu

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 9041 - 9058

Published: Nov. 1, 2024

Lung diseases are associated with high morbidity and mortality rates, thereby jeopardizing human health imposing a great burden on society. Currently, lung mainly treated medications, oxygen therapy mechanical ventilation, but these approaches unable to effectively reduce the rate. Therefore, transplantation remains ultimate treatment for various chronic diseases, this is also hindered by limited availability of sources, immature technology low survival rate after transplantation. With constant changes in environment, pathogens, type amount harmful substances prevalence respiratory there an urgent need identify alternative methods. Research stem cell has been very successful recent years, mesenchymal cells (MSCs), together their secretory bodies, play significant therapeutic role. Extracellular vesicles MSCs (MSC-EVs) major components paracrine secretion MSCs, including exosomes, microvesicles, apoptotic among which exosomes most typical. MSC-EVs believed be present tissues body where they can carry proteins, DNA, RNA biologically active factors, just name few. They transmit biological signals participate different activities, maintenance homeostasis within tissue. Several studies have further demonstrated that generated extracellular important role diseases. In paper, origin, properties roles reviewed, mechanisms limitations current options Chronic Obstructive Pulmonary Disease, asthma, infectious disease, cancer, pulmonary fibrosis, arterial hypertension, acute injury/ distress syndrome discussed (Figure 1). addition, possible future research directions view providing new ideas

Language: Английский

Citations

2
Diseased Tendon Models Demonstrate Influence of Extracellular Matrix Alterations on Extracellular Vesicle Profile DOI Creative Commons

Kariman A. Shama,

Zachary Greenberg,

Chadine Tammame

et al.

Bioengineering, Journal Year: 2024, Volume and Issue: 11(10), P. 1019 - 1019

Published: Oct. 12, 2024

Tendons enable movement through their highly aligned extracellular matrix (ECM), predominantly composed of collagen I. Tendinopathies disrupt the structural integrity tendons by causing fragmentation fibers, disorganization fiber bundles, and an increase in glycosaminoglycans microvasculature, thereby driving apparent biomechanical regenerative capacity patients. Moreover, complex cellular communication within tendon microenvironment ultimately dictates fate between healthy diseased tendon, wherein vesicles (EVs) may facilitate tendon's transporting biomolecules tissue. In this study, we aimed to elucidate how EV functionality is altered context microenvironments using polycaprolactone (PCL) electrospun scaffolds mimicking pathological matrices. Scaffolds were characterized for alignment, mechanical properties, activity. EVs isolated analyzed concentration, heterogeneity, protein content. Our results show that our mimicked led secretion baseline metabolic activity over where reduced a significant 5 days observed. These findings suggest scaffold mechanics influence functionality, offering insights into homeostasis. Future research should further investigate cargo affects microenvironment.

Language: Английский

Citations

1